CHM 102 Introductory Organic Chemistry Notes PDF

08/12/2022 Nomenclature of Carboxylic Acids CHM 1...

08/12/2022 Nomenclature of Carboxylic Acids CHM 102 Formula HCO2H IUPAC Name Methanoic acid Common Name Formic acid Source Ants (L. formica) INTRODUCTORY ORGANIC CH3CO2H Ethanoic acid Acetic acid Vinegar (L. acetum) CHEMISTRY CH3CH2CO2H CH3(CH2)2CO2H Propanoic acid Butanoic acid Propionic acid Butyric acid Milk (Gk. Protus prion) Butter (L. butyrum) CH3(CH2)3CO2H Pentanoic acid Valeric acid Valerian root CH3(CH2)4CO2H Hexanoic acid Caproic acid Goats (L. caper) Dr (Mrs) A. D. Adesina CH3(CH2)5CO2H Heptanoic acid Enanthic acid Vines (Gk. Oenanthe) CH3(CH2)6CO2H Octanoic acid Caprylic acid Goats (L. caper) CH3(CH2)7CO2H Nonanoic acid Pelargonic acid Pelargonium (an herb) CH3(CH2)8CO2H Decanoic acid Capric acid Goats (L. caper) L. Latin name, Gk. Greek name Br Chemistry of carboxylic acids, amines and their CH3 H O 4 5 4 3 H2 1 derivatives H3C C C 2 C C H3C 3 2 1 CH CO2H Carboxylic Acids O H CH3 C2H5 CH3 The carboxyl functional group is made up of a hydroxyl group 2-ethyl-4,4-dimethylpentanoic acid 2-bromo-3-methylbutanoic acid bonded to a carbonyl group. 1 CO2H COOH It is often written in condensed form as RCO2H or RCOOH H2N 2 H O 3 H OH R C 4 CH3 Many carboxylic acids are found in nature O H 2-amino-3-hydroxybutanoic acid Benzoic acid 1  08/12/2022 Simple dicarboxylic acids having the general formula HO2C-(CH2)n-CO2H Preparation of Carboxylic acids (where n = 0 to 5) are known by the common names: 1. Oxidation of Arene side-chains 3. Oxidation of aldehydes Oxalic (n = 0), Malonic (n = 1), Succinic (n = 2), Glutaric (n = 3), Adipic (n = 4) HO2C CO2H H3C C2H5 and Pimelic (n = 5) acids KMnO4 O O O O H2O, heat Tollen's reagent C C Some naturally occurring carboxylic acids CH2CH2CH3 CO2H H Ag2O, NH4OH OH CO2H H C OH O CO2H CO2H 2. Oxidation of primary alcohols 4. Oxidative cleavage of Alkenes and HO CO2H O Alkynes CH2 Jones' reagent H3C CO2H CH3(CH2)8CH2OH CH3(CH2)8COH H R O N CO2H KMnO4 CO2H H2CrO4 C C or R 2 R C C C R H2O, heat malic acid pyruvic acid niacin citric acid R H OH (various fruits) (a metabolic intermediate) a vitamin (from citrus fruits) Give IUPAC names for the following Draw structures corresponding to 5. Hydrolysis of Nitriles compounds O the following IUPAC names H 2O + H 3O + H2 (a) (CH3)2CHCH2COOH R H2 C Br NaCN R H2 C C N R C C + NH4+ SN 2 heat (b) CH3CH CHCH CHCOOH (a) 2,3-Dimethylhexanoic acid OH (c) CH CHCH CH COOH (b) 4-Methylpentanoic acid 6. Carboxylation of Organometallic Reagents 3 2 2 (c) trans-1,2-cyclobutanedicarboxylic O Br Mg 1) CO2 R R Mg Br R C + Mg(OH)Br acid Br 2) H3O+ (d) CH3 ether Grignard reagent OH (d) o-Hydroxybenzoic acid O COOH Li Br C 1) CO2 2 Li OH pentane 2) H3O+ + LiBr or ether (phenyl lithium) 2  08/12/2022 O Reactions of Carboxylic Acids (b) O CH3 H C 1. Salt formation H C + N toluene N + H2O 110 °C Because of their enhanced acidity, carboxylic acids react with bases to form OH H H3C ionic salts. amide RCOOH + NaHCO3 RCOONa + CO2 + H2O (c) O O O RCOOH + (CH3)3N RCOO(CH3)3NH heat 6 F3 C C + P2 O 5 3 F3C C C CF3 + 2 H3PO4 2. Reduction OH O acid anhydride Carboxylic acids are reduced by LiAlH4 (but not by NaBH4) to yield primary O (d) O alcohols. 1. LiAlH4, THF H2SO4 H3C C + H 2O RCOOH RCH2OH H 3C C + C2H5OH 2. H3O+ O C2H5 OH ester 3. Substitution of the hydroxyl group Chemistry of Amines Reactions in which the hydroxyl group of a carboxylic acid is replaced Amines are organic derivatives of ammonia. They contain a nitrogen atom by another nucleophilic group are important for preparing functional with a lone pair of electrons, making amines both basic and nucleophilic. derivatives of carboxylic acids. The terms primary (1°), secondary (2°) and tertiary (3°) are used to classify amines. They refer to the number of alkyl (or aryl) substituents bonded to (a) O the nitrogen atom. O H2 CH3 SOCl2 H2 H3C C CH3 H2 O2 N C + HCl + SO2 H3C C NH2 O2 N C C N H3C C N heat C C H2 Cl H2 H2 OH CH3 H acyl chloride butanamine N-methylpropanamine N,N-dimethylethanamine 1° amine 2° amine 3° amine 3  08/12/2022 A nitrogen bonded to four alkyl groups will necessarily be positively Amines with more than one functional group are named by considering charged, and is called a 4°-ammonium cation. For example, (CH3)4N+Br- the –NH2 as an amino substituent on the parent molecule: is tetramethylammonium bromide. COOH Amines occur widely throughout both plants and animals. For instance, NH2 triethylamine occurs in animal tissues and is partially responsible for NH2 O the distinctive odour of many fish: quinine is an important antimalarial CH3CH2CHCOOH H2N CH2CH2CCH3 drug isolated from the bark of the South American Cinchona tree; and NH2 codeine is an analgesic (painkiller) found in the opium poppy. 2-Aminobutanoic acid 2,4-Diaminobenzoic acid 4-Amino-2-butanone Nomenclature of Amines NH2 CH3 Properties of Amines H2N CH2CH2CH2CH2 NH2 H3C C NH2 Amines with fewer than five carbon atoms are generally water-soluble. CH3 Primary and secondary amines form hydrogen bonds and are highly 1,4-Butanediamine Cyclohexylamine tert-Butylamine associated. Many aromatic and heterocyclic amines are known by unique common Another characteristic of amines is their odour. Low-molecular-weight names. amines such as triethylamine have a distinctive fishlike aroma. NH2 Amines are considerably more basic than alcohols, ethers, or water. N N N In addition to their behaviour as bases, primary and secondary amines can N H H H also act as very weak acids because an N-H proton can be removed by a aniline piperidine pyridine pyrrolidine pyrrole sufficiently strong base. 4  08/12/2022 Preparation of Amines Reactions of Amines 1. Reduction of Nitriles: the two-step sequence of SN2 displacement with CN- followed by reduction is an excellent method for converting an alkyl 1. Alkylation and Acylation: reaction with alkyl halides or acyl chlorides halide into a primary alkylamine having one more carbon atom. O O NaCN 1. LiAlH4, ether RX RCN RCH2NH2 Pyridine C R' 2. H2O C + R'NH2 R N + HCl Alkyl halide Nitrile 1° amine solvent R Cl 2. Reduction of Amides: Amide reduction provides excellent method for H converting carboxylic acids and their derivatives into amines with the same number of carbon atoms. 2. Hofmann Elimination: amines can be converted into alkenes by an O elimination reaction. O 1. LiAlH4, ether CH3I Ag2O 1. SOCl2 CH3(CH2)5NH2 CH3(CH2)5N(CH3)3I CH3(CH2)3CH CH2 + N(CH3)3 R C OH R C NH2 RCH2NH2 excess H2O, heat 2. NH3 2. H2O Hexylamine 1-Hexene Carboxylic acid Amide 1° amine 3. Reduction of Nitro Compounds: Arylamines are usually prepared by Carboxylic Acid Derivatives nitration of an aromatic starting material, followed by reduction of the These are compounds in which the acyl group (RCO-) is bonded to an nitro group. NO2 electronegative atom or substituent Y that can act as a leaving group in a NH2 substitution reaction. + 1. SnCl2, H3O They are usually prepared by replacement of the hydroxyl group in 2. NaOH, H2O carboxylic acids with substituents such as halo, alkoxyl, amino and acycloxy. CHO CHO The chemistry of all acid derivatives is similar and is dominated by the m-Nitrobenzaldehyde m-Aminobenzaldehyde nucleophilic acyl substitution reaction. 5  08/12/2022 Amides: the name of the related acid is used first and the oic or ic acid suffix is O O O O replaced by amide (only for 1° amides). e.g. CH3CONH2 is ethanamide. 2° and C C C C 3° amides have alkyl substituents on the nitrogen atom. These are designated R OH R X R O R' by “N-alkyl” term(s) at the beginning of the name e.g. CH3(CH2)2CONHC2H5 is Acyl halide N-ethylbutanamide and HCON(CH3)2 is N,N-dimethylmethanamide (or N,N- Carboxylic acid (X = F, Cl, Br, I) Acid anhydride dimethylformamide). Cyclic amides are called lactams. O O Nitriles: simple acyclic nitriles are named by adding nitrile as a suffix to the C C R C N name of the corresponding alkane (same number of carbon atoms). Chain R OR' R NH2 numbering begins with the nitrile carbon e.g. (CH3)2CHCH2CN is 3- Ester Amide Nitrile methylbutanenitrile. Nomenclature Preparation Esters: the alkyl group is named first, followed by a derived name for 1. Acyl Halides: Carboxylic acids are converted into acyl chlorides by the acyl group, the oic or ic suffix in the acid name is replaced by ate. treatment with thionyl chloride (SOCl2); and into acyl bromides by e.g. CH3(CH2)2COOC2H5 is ethyl butanoate treatment with phosphorus tribromide (PBr3). Cyclic esters are called lactones. O OH O Cl C C Acyl Halides: the acyl group is named first, followed by the halogen H3C CH3 name as a separate word e.g. CH3CH2COCl is propanoyl chloride H3C CH3 SOCl2 Acid Anhydrides: the name of the related acid is used first, followed by CHCl3 + HCl + SO2 the separate word “anhydride”. e.g. CH3COOCOCH2CH3 is ethanoic propanoic anhydride CH3 CH3 6  08/12/2022 4. Amides: Amides are difficult to prepare by direct reaction of carboxylic 2. Acid Anhydrides: they are derived from two molecules of carboxylic acid acids with amines because amines are bases that convert acidic carboxyl by heating to remove 1 equivalent of water. groups into their carboxylate anions. O O Cyclic anhydrides with 5- or 6- membered rings are obtained by high- NH3 C C temperature dehydration of the diacids. R OH R ONH4 O COOH H2C C Amides are usually prepared by reaction of an acid chloride with an amine. H 2C O Ammonia, monosubstituted amines, and disubstituted amines all undergo H2C 200 °C H2C COOH C the reaction. O O O NH3 Succinic acid C C Succinic anhydride R Cl R NH2 3. Esters Reactivity (a) The SN2 reaction of a carboxylate anion with a 1° alkyl halide Electronically, strongly polarised acid derivatives react more readily than less O O polar ones. Thus, acyl halides are more reactive than esters, which are more SN 2 CH3(CH2)2CONa + H3C I CH3(CH2)2COCH3 + NaI reactive than amides, because the electronegative chlorine polarises the reaction (b) The nucleophilic acyl substitution reaction of a carboxylic acid with an carbonyl group more than does an alkoxyl group or an amino group. OH alcohol. OH In homogeneous solvent systems, reaction of acyl chlorides with water occurs CH O CH O rapidly, and does not require heating or catalysts. Amides, on the other hand, C C + CH3CH2OH HCl react with water only in the presence of strong acid or base catalysts and OH OCH2CH3 external heating. Mandelic acid Ethanol Ethylmandelate Acyl Halides > Anhydrides > Esters > Amides 7  08/12/2022 Reactions of Carboxylic Acid Derivatives 4. Reduction: acyl chlorides are reduced by LiAlH4 to yield primary alcohols. O Acyl Halides C CH2OH 1. Hydrolysis: acyl halides react with water to yield carboxylic acids Cl 1. LiAlH4, ether O O 2. H3O+ OH2 + HCl C C Benzoyl chloride Benzyl alcohol R Cl R OH Since HCl is generated during the hydrolysis, the reaction s often carried out in 5. Reaction with Organometallic reagents: Grignard reagents react with acyl the presence of a base such as pyridine or NaOH to remove the HCl and chlorides to yield tertiary alcohols in which two of the substituents are the O R' R' prevent it from causing side reactions. same. 1. Ether solvent + 2 R'MgX C C 2. H3O+ R OH R Cl Acyl chloride 3° Alcohol Acid Anhydrides 2. Alcoholysis: acyl halides react with alcohols to yield esters. O The chemistry of acid anhydrides is similar to that of acid chlorides. Although O C OH anhydrides react more slowly than acid chlorides, the kinds of reactions the C Cl Pyridine + O two groups undergo are the same. Benzoyl chloride Cyclohexanol 1. Hydrolysis: acid anhydrides react with water to form acids Cyclohexyl benzoate O O O 3. Aminolysis: acyl halides react rapidly with ammonia and amines to give C C H2O C R O R' R OH amides in good yield. Mono- and disubstituted amines can be used, but not 2. Alcoholysis: acid anhydrides react with alcohols to form esters trisubstituted amines (R3N). O O O O O (CH3)2CHCCl + 2 NH3 (CH3)2CHCNH2 + NH4Cl C C R'OH C 2-methylpropanoyl 2-methylpropanamide chloride R O R R OR' 8  08/12/2022 3. Aminolysis: acid anhydrides react with amines to form amides 3. Reduction: conversion of esters into alcohols. Esters are easily reduced by H treatment with LiAlH4 to yield primary alcohols. N O NH2 O O O NaOH C C LiAlH4, ether + CH3 H3CH2CHC CHCH2OH + CH3CH2OH H3C O CH3 H 2O H3CH2CHC CHCOCH2CH3 HO HO H3O+ + CH3COOH 4. Reaction of Organometallic reagents: esters and lactones react with 2 equivalents of a Grignard reagent to yield a 3° alcohol with two identical 4. Reduction: acid anhydrides are reduced by LiAlH4 to yield primary alcohols substituents. O OH O O O H H 1. 2 PhMgBr 2 C Ph C Ph C C C 2 C 2. H3O+ [H] [H] Ph OCH3 R O R R H R OH Ph Esters Amides 1. Hydrolysis: conversion of esters into carboxylic acids. Esters are 1. Amides undergo hydrolysis to yield carboxylic acids plus amine on hydrolysed, either by aqueous base or by aqueous acid, to yield carboxylic heating in either aqueous acid or aqueous base. acids plus alcohols. Ester hydrolysis in basic solution is called O O 2. Reduction: conversion of amides into amines: like other carboxylic acid saponification. H2O, NaOH C or H3O+ C + R'OH derivatives, amides can be reduced by LiAlH4. The product of the R OR' R OH reduction, however, is an amine rather than an alcohol. The amide 2. Aminolysis: conversion of esters into amides. Esters react with ammonia carbonyl group is thus converted into a methylene group (C=O → CH2). and amines to yield amides. O O C C OCH3 NH3 NH2 + CH3OH Ether 9